Fecal Microbiota Transplantation in Patients With Active Ulcerative Colitis: Restoration of the Microbiome Through Superdonor Selection
试验速览
- 阶段
- 不适用
- 入组人数
- 108
- 试验地点
- 2
- 主要终点
- steroid-free clinical remission
研究概览
简要总结
The AIM of this study is to investigate whether the FMT success rate in active UC patients can be increased by intensive donor pre-screening, anaerobic preparation of the FMT and by repeated FMT.
The investigators will start a national multi-centre double-blind randomized sham-controlled trial in April 2017 at 6 hospitals in Belgium and 2 in The Netherlands. They will randomly allocate 108 patients with active ulcerative colitis (Mayo score 4-10, endoscopic Mayo score 2 or 3) in a 1:1 ratio, using a pre-established randomization list, to either 'superdonor' faecal microbiota transplantation or autologous fecal microbiota transplantation (=sham). Each patient will receive 4 FMT's. At baseline FMT will be performed during sigmoidoscopy. At week 1, 2 and 3, the FMT will be administered through rectal instillation. Each FMT will be derived from one donor. Donors will be pre-selected based on a species richness and abundance of taxa of interest. The primary outcome will be steroid-free clinical and endoscopic remission at week 8 (Mayo score ≤2, all subscores ≤ 1, and ≥1 point reduction in endoscopy subscore). Fecal, blood and mucosal samples and questionnaires will be collected at different time points. 16S rRNA stool analysis will be performed to assess the microbial changes after FMT.
详细描述
Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD) characterized by a diffuse mucosal inflammation, extending proximally from the rectum and causing symptoms of bloody diarrhea. The complex pathogenesis of IBD remains largely unknown.
Manipulation of the enteric microbiota to restore normobiosis has therapeutic potential in IBD. Fecal microbiota transplantation (FMT), whereby fecal microbiota from a healthy donor is transplanted to a patient, is being studied as therapy for active UC patients. Currently three randomized controlled FMT trials have been published in patients with active ulcerative colitis with increasing success9-11. The investigators feel that the FMT success rate in active UC patients can be improved by solving the remaining pressing questions including the use of selected donors, preparation of the FMT, mode and frequency of administration. The investigators therefore designed a new multicenter interventional study with FMT to specifically answer these questions.
The overall main aims of this project are:
Objective 1: They want to examine whether the FMT success rate in active UC patients can be increased by strictly pre-selecting the donors, by standardizing and optimizing the FMT preparation and by repeated FMT administration.
Objective 2: The investigators want to investigate the temporal and functional changes of the intestinal microbiota of UC patients after FMT
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age >18 years
- •Patients with currently mild-moderate active ulcerative colitis (defined by endoscopic Mayo sub score 2-3 and a Total Mayo score between 4-10)
- •Provide written informed consent to participate as shown by a signature on the consent form.
- •Patients on concomitant UC-therapy are allowed if the concomitant treatment is restricted to current treatment and at a stable dose (not in the induction faze).
- •Topical therapy and trial medication is not allowed.
- •A maximum dose of 15mg methylprednisolone.
- •Negative coproculture (Salmonella, Shigella, Yersinia, Campylobacter, Entamoeba histoliytica, Clostridium difficile toxins and enteropathogenic E. coli)
- •Women need to use reliable contraceptives during participation in the study
排除标准
- •Consent not obtained or unable to give informed consent
- •Condition leading to profound immunosuppression
- •For example: HIV, infectious diseases leading to immunosuppression, bone marrow malignancies, liver cirrhosis
- •Use of systemic chemotherapy
- •Use of antibiotics in the previous 4 weeks
- •Surgery: Total colectomy, presence of a stoma or ileo-anal pouch
- •Presence of an intra-abdominal fistula
- •Colon carcinoma
- •Diverticulitis
- •Patients who are steroid dependent and requiring >15mg methyl prednisone 2 week before START.
- •Detection of a gastrointestinal pathogen on stool analysis
- •A diagnosis of Crohn's disease of indeterminate colitis
- •Females who are pregnant or actively trying to fall pregnant
研究组 & 干预措施
Superdonor FMT
Fecal microbiota transplantation from a healthy donor that was selected based on a fecal/blood screening, medical interview and on abundance of taxa of the investigators their interest
干预措施: superdonor FMT (Other)
Autologous FMT
Fecal microbiota transplantation derived from feces from the patient her/himself.
干预措施: autologous FMT (Other)
结局指标
主要结局
steroid-free clinical remission
时间窗: Week 8
defined as a total Mayo score of 2 or less and with all Mayo subscores of 1 or less.
steroid-free endoscopic remission or response
时间窗: Week 8
defined as at least a 1 point reduction from baseline in the endoscopy subscore.
次要结局
- the investigation of changes in blood and fecal inflammatory markers before and after FMT(Week 8)
- Steroid-free clinical remission(Week 8)
- Steroid-free clinical response(Week 8)
- Steroid-free endoscopic response(Week 8)
- Steroid-free endoscopic remission(Week 8)
研究者
Clara Caenepeel
PhD-student under supervision of Prof. Dr. Séverine Vermeire
Universitaire Ziekenhuizen KU Leuven